Core C supports Projects 1, 2, and 3 by (1) preparing radiolabeled antibodies for preclinical and clinical studies; (2) translating Project 3 chemistry to standard operation methods to conjugate and radiolabel radiopharmaceuticals with optimized yields and quality; (3) assisting in the selection of Project 3 reagents for human pharmaceutical development on the basis of evaluation in mice; and (4) record keeping in accordance with FDA and radiation use regulatory agencies. During the current funded period, Core C developed simplified procedures to radiolabel MoAbs with Y-90 with yields and radiopharmaceutical quality comparable to 131l- MoAbs, using macrocyclic chelating agents developed in Project 3. Core C has also performed evaluations of DOTA-peptide chelating agents under development in Project 3. The chelating agents incorporate peptide linkers which remain uncleaved in circulation and at the tumor target, but should be readily cleaved intracellularly and clear the liver, kidney, and other non-target sites. Digestion of a prototypical DOTA-peptide chelate was demonstrated in vitro and improved clearance from the liver was subsequently demonstrated in the tumored mouse model and in pilot clinical studies. A library of new peptide linkers has been generated in Project 3, and three linkers subject to digestion have been identified. Core C has demonstrated the stability of the linkers in vitro in human plasma and has performed autoradiography studies of one peptide in mice that demonstrated favorable biodistribution. The proposal for Core C includes preparing radiopharmaceuticals for Project 1 and 2 preclinical and clinical studies, using simplified, high yield procedures already developed to minimize expense and radiation exposure. Core C will continue to evaluate DOTA-peptide chelating agents from the existing and proposed combinatorial libraries in Project 3 by biodistribution studies in the tumored mouse model, to assess tumor uptake and hepatic, renal, and total body clearance. The peptide(s) exhibiting the most favorable bjodistribution results according to predetermined, statistically evaluable criteria for radiation dose to liver, kidneys, and tumor, will be examined further for characterization of metabolites. Core C will continue to develop conjugation, radiolabeling , and purification of MoAb fragments and peptides to prepare novel radiopharmaceuticals.